Biochemistry major in need of help!

Larry Hunter hunter at work.nlm.nih.gov
Wed Feb 20 17:04:04 EST 1991



   As I'm interested in neuro/psychopharmacology, I thought I could
   talk about something like DNA synthesis, RNA translation, or
   protein function in models of learning and memory. Unfortunately,
   I'm having trouble finding any articles referencing this, although
   several professors have claimed this shouldn't be a problem...

Well, there is not a great deal known about this topic yet, although
there is some exciting research.  I'm not an expert in the field, but
I have tried to keep up with what's happening. I would recommend
investigating two lines of research.  One is Eric Kandel's work with
the sea slug Aplysia.  Try:

TI  - 5-HT modulates protein synthesis and the expression of specific
      proteins during long-term facilitation in Aplysia sensory
      neurons.
AU  - Barzilai A
AU  - Kennedy TE
AU  - Sweatt JD
AU  - Kandel ER
SO  - Neuron 1989 Jun;2(6):1577-86
AB  - Long-term, but not short-term, facilitation induced by 5-HT in
      Aplysia sensory neurons is blocked by application of inhibitors
      of protein synthesis or RNA synthesis during the 1.5 hr training
      period. These findings suggest that genes and proteins not needed
      for the short-term process are required for long-term
      facilitation. To identify these proteins, we examined changes in
      overall and specific protein synthesis in sensory neurons. During
      the 1.5 hr period of stimulation, 5-HT initiated three temporally
      distinct changes in total protein synthesis: a small decrease at
      0.5 hr, a small increase at 1 hr, and a second and larger
      increase at 3 hr. 5-HT also produced three temporally distinct
      changes in the synthesis of individual proteins that could be
      resolved on 2-D gels. First, there was an increase at 30 min in
      the rate of synthesis of 10 proteins and a decrease in the
      synthesis of 5 proteins. These changes in protein expression are
      rapid and transient, subsiding within 1-3 hr, and are
      transcription-dependent. Second, at 3 hr, there is a transient
      increase in 4 different proteins that also is
      transcription-dependent and lasts approximately 5 hr. Finally, at
      24 hr, during the retention phase of facilitation, there was a
      sustained increase in the expression of two proteins.

There are several follow up papers, but this is a good place to start.
You also might want to look for the work of one of Kandel's students,
Tom Carew.

The other place to look is in the literature of cognitive defects
introduced by mutations.  There are a set of so-called "dunce" genes
that have been identified in Drosophila, C. elegans, and other
organisms.  Try:

TI  - Cloning and characterization of mammalian homologs of the
      Drosophila dunce+ gene.
AU  - Davis RL
AU  - Takayasu H
AU  - Eberwine M
AU  - Myres J
SO  - Proc Natl Acad Sci U S A 1989 May;86(10):3604-8
AB  - A probe representing the Drosophila dunce+ (dnc+) gene, the
      structural gene for a cAMP phosphodiesterase (PDEase), detects
      homologous sequences in many different organisms, including
      mouse, rat, and human. Genomic and cDNA clones representing a
      homolog of the Drosophila dnc+ gene were isolated from rat
      libraries and characterized. This gene has been named ratdnc-1.
      One cDNA clone defines a large open reading frame of
      approximately 1.8 kilobases (kb), predicting a protein sequence
      of 610 amino acids with significant homology to a conserved
      domain of approximately 275 residues found in most other PDEases.
      The amino acid identity value to the Drosophila cAMP PDEase
      within this domain is a striking 75%. Other cDNA clones show
      blocks of sequence divergence from this cDNA clone close to the
      predicted N terminus, indicating the potential existence of a
      family of related enzymes encoded by alternatively spliced
      messenger RNAs from ratdnc-1. Genomic blotting experiments
      suggest the existence of at least one other rat gene with
      homology to ratdnc-1. RNAs homologous to ratdnc-1 are
      heterogeneous in size between tissues, with heart containing a
      major transcript of 4.4 kb and brain one of 4.0 kb. The potential
      identity of the product of the ratdnc-1 gene with known PDEases
      is discussed.

I would also recommend chapter 8 of L.S. Seiden and L.A. Dykstra's
"Psychopharmacology: A Biochemical and Behavioral Approach," (Van
Nostrand, 1977) which, although somewhat dated, has a nice overview of
the pharmacological and biochemical aspects of learning and memory.

Hope this helps....

		Larry Hunter (Another computer scientist interested in
	  		      learning and memory in biological systems)

--
Lawrence Hunter, PhD.
National Library of Medicine
Bldg. 38A, MS-54
Bethesda. MD 20894
(301) 496-9300
(301) 496-0673 (fax)
hunter at nlm.nih.gov (internet)
hunter%nlm.nih.gov at nihcu (bitnet/earn)



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